Nicola Tinari

University of Chieti-Pescara

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i-10 index

Research Trends

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Document Type

Co-Authors

Clara Natoli

University of Chieti-Pescara

118

Antonino Grassadonia

University of Chieti-Pescara

100

Stefano Iacobelli

CTI BioPharma (Italy)

Michele De Tursi

University of Chieti-Pescara

Patrizia Vici

Istituti di Ricovero e Cura a Carattere Scientifico

Rossano Lattanzio

University of Chieti-Pescara

Paolo Marchetti

Sapienza University of Rome

Teresa Gamucci

Ospedale Sandro Pertini

Davide Brocco

University of Chieti-Pescara

Laura Pizzuti

Istituti di Ricovero e Cura a Carattere Scientifico

Cooperative Institutions

Istituti di Ricovero e Cura a Carattere Scientifico

302

University of Chieti-Pescara

279

Sapienza University of Rome

114

University of L'Aquila

104

Ospedale SS. Annunziata

102

University of Naples Federico II

Università Cattolica del Sacro Cuore

Fondazione IRCCS Istituto Nazionale dei Tumori

National Cancer Institute

Presidio Ospedaliero

Author Statistics

Papers

Citation

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i-10 index

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Timed flat infusion of 5-fluorouracil increases the tolerability of 5-fluorouracil/docetaxel regimen in metastatic breast cancer: a dose-finding study

British Journal of Cancer (2004)

Corrado Ficorella Micaela Morelli Enrico Ricevuto Katia Cannita Giampiero Porzio

A dose-finding study was undertaken to determine the maximum-tolerated dose, and the recommended dose of docetaxel in combination with 12-h timed (22:00–10:00) flat infusion of 5-fluorouracil (5-FU) in metastatic breast cancer patients. This schedule seems to reduce the occurrence of stomatitis of the docetaxel and infusional 5-FU regimen.

Regimen

Tolerability

10.1038/sj.bjc.6601971

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Citations (3)

Supplementary Online Material from 3D-Informed Targeting of the Trop-2 Signal-Activation Site Drives Selective Cancer Vulnerability

Emanuela Guerra Marco Trerotola Valeria Relli Rossano Lattanzio Romina Tripaldi

<p>Supplementary Online Material</p>

Vulnerability

SIGNAL (programming language)

10.1158/1535-7163.23274909

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Citations (0)

Data from 3D-informed targeting of the Trop-2 signal-activation site drives selective cancer vulnerability

Emanuela Guerra Marco Trerotola Valeria Relli Rossano Lattanzio Romina Tripaldi

<div>Abstract<p>Next-generation Trop-2-targeted therapy against advanced cancers is hampered by expression of Trop-2 in normal tissues. We discovered that Trop-2 undergoes proteolytic activation by ADAM10 in cancer cells, leading to the exposure of a previously inaccessible protein groove flanked by two N-glycosylation sites. We designed a recognition strategy for this region, to drive selective cancer vulnerability in patients. Most undiscriminating anti-Trop-2 monoclonal antibodies (mAb) recognize a single immunodominant epitope. Hence, we removed it by deletion-mutagenesis. Cancer-specific, glycosylation-prone mAb were selected by ELISA, bio-layer interferometry, flow cytometry, confocal microscopy for differential binding to cleaved/activated, wild-type and glycosylation-site-mutagenized Trop-2. The resulting 2G10 mAb family binds Trop-2-expressing cancer cells, but not Trop-2 on normal cells. We humanized 2G10 by state-of-the-art CDR grafting/re-modeling, yielding Hu2G10. This antibody binds cancer-specific, cleaved/activated Trop-2 with Kd <10-12 M, and uncleaved/wtTrop-2 in normal cells with Kd 3.16x10-8 M, thus promising an unprecedented therapeutic index in patients. In vivo, Hu2G10 ablates growth of Trop-2-expressing breast, colon, prostate cancers, but shows no evidence of systemic toxicity, paving the way for a paradigm shift in Trop-2-targeted therapy.</p></div>

Vulnerability

SIGNAL (programming language)

10.1158/1535-7163.c.6653601.v3

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Citations (0)

Correlations Between the Immune-related Adverse Events Spectrum and Efficacy of Anti-PD1 Immunotherapy in NSCLC Patients

Clinical Lung Cancer (2019)

Alessio Cortellini Rita Chiari Biagio Ricciuti Giulio Metro Fabiana Perrone

Atezolizumab

Cancer Immunotherapy

Broad spectrum

10.1016/j.cllc.2019.02.006

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Citations (148)

Low Phosphatidylserine+ Cells Within the CD34+/CD45dim/CD117(c-kit)+ Subpopulation are Associated with Poor Outcomes in Metastatic Colorectal Cancer

Cancers (2025)

Davide Brocco Pasquale Simeone Pietro Di Marino Domenico De Bellis Francesca D’Ascanio

Background: Colorectal cancer is among the most prevalent causes of tumor-related deaths worldwide. Antiangiogenic therapy represents a cornerstone of metastatic CRC treatment, and biomarkers are advocated for the optimization of this therapeutic strategy. Methods: In this observational prospective study, we employed an optimized flow cytometry protocol to investigate the prognostic and predictive potential of blood circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs), and related subsets in a cohort of patients with metastatic colorectal cancer (n = 40). Results: Computational FC analysis revealed a differential enrichment of blood cell clusters with a CD34+/CD45dim/CD117(c-kit)+ phenotype between responders and non-responders both to antiangiogenic and non-antiangiogenic treatments. Intriguingly, our results show that a high percentage of annexin V-negative cells in a putative circulating progenitor population with a CD34+/CD45dim/CD117+ phenotype was correlated with a reduced response to systemic anticancer treatments (p = 0.015) and worse overall survival (log-rank p = 0.03). In addition, we observed increased blood concentrations of CD34+/CD45dim/CD117+/annexin V- cells in patients with a higher number of metastatic sites (p = 0.03). Conclusions: Overall, these findings hold promise for the identification of novel circulating biomarkers to develop more personalized treatment approaches in patients with metastatic colorectal cancer.

CD117

Circulating tumor cell

10.3390/cancers17030499

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Galectin-3 overexpression protects from apoptosis by improving cell adhesion properties

International Journal of Cancer (2000)

Paola Matarrese O. Fusco Nicola Tinari Clara Natoli Fu‐Tong Liu

Galectin-3 is a carbohydrate-binding protein endowed with affinity for β-galactosides. It plays a role in cell–cell and cell–matrix interactions. Furthermore, it has been hypothesized to be involved in tumor progression and metastasis. To address the role of galectin-3 in the invasive and metastatic processes, we stably overexpressed galectin-3 in human breast carcinoma cell lines, and we evaluated the influence of elevated galectin-3 expression on several cell features, including cellular homotypic and heterotypic interactions and cell survival. No differences in various parameters related with cell growth features and proliferation were detected. By contrast, we found that galectin-3 overexpressing cells, with respect to low galectin-3 expressing cells, exerted: (1) a significantly enhanced adhesion to laminin, fibronectin and vitronectin exerted both directly or via increased expression of specific integrins, e.g., alpha-4 and beta-7; (2) a remodeling of those cytoskeletal elements associated with cell spreading, i.e., microfilaments; (3) an enhanced survival upon exposure to different apoptotic stimuli, such as cytokine and radiation. Collectively, our results indicate that overexpression of galectin-3 may play a role in tumor cell invasion and metastasis by specifically influencing cell adhesion to the extracellular matrix. This may confer selective survival advantage and resistance to the particular homeless-induced apoptosis called anoikia. Int. J. Cancer 85:545–554, 2000. © 2000 Wiley-Liss, Inc.

Galectin-3

Galectin

Galectin-1

10.1002/(sici)1097-0215(20000215)85:4<545::aid-ijc17>3.3.co;2-e

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Citations (20)

Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

Thoracic Cancer (2019)

Alessio Cortellini Lucilla Verna Giampiero Porzio Federico Bozzetti Pierpaolo Palumbo

Sarcopenia represents one of the hallmarks of all chronic disease, including non‐small cell lung cancer (NSCLC). A computed tomography scan is an easy modality to estimate the skeletal muscle mass through cross‐sectional image analysis at the level of the third lumbar vertebra (L3). Baseline skeletal muscle mass (SMM) was evaluated using gender‐specific cutoffs for skeletal muscle index in NSCLC patients administered immunotherapy with nivolumab to evaluate its possible correlations with clinical outcomes. From April 2015 to August 2018, 23 stage IV NSCLC patients were eligible for image analysis. Nine patients (39.1%) had low SMM. Among patients with baseline low and non‐low SMM, median progression free survival was 3.1 and 3.8 months, respectively ( P = 0.0560), while median overall survival was 4.1 and 13 months, respectively ( P = 0.2866). This hypothesis‐generating preliminary report offers the opportunity to speculate about the negative influence of sarcopenia on immune response. In our opinion, nutritional status could affect the clinical outcomes of immunotherapy, even if we cannot make definitive conclusions here. Further studies on the topic are required.

Value (mathematics)

10.1111/1759-7714.12965

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Citations (58)

Membranous Nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal-A early breast cancer

Oncogenesis (2014)

Rossano Lattanzio Reza Ghasemi Francesco Brancati Rossana La Sorda Nicola Tinari

Nectins are Ca(2+)-independent immunoglobulin-like cell adhesion molecules that compose a family of four members that regulate several cellular activities such as movement, proliferation, survival, differentiation, polarization, and the entry of viruses. Nectin-4 has recently emerged as a metastatis-associated protein in several cancers. Here, we have evaluated the association between the expression of Nectin-4 and the clinical outcome of patients with node-negative, T1/T2 breast cancers.The study group consisted of 197 patients presenting with primary unilateral breast carcinoma (T1/T2), with no evidence of nodal involvement and distant metastases. Nectin-4 protein expression was assessed by immunohistochemistry on tissue microarrays, and the results correlated with the clinical data using Kaplan-Meier curves and multivariate Cox regression analysis. Thirty-four out of 197 tumors (17.3%) exhibited Nectin-4 expression on cell membrane (m-Nectin-4) and 122 out of the 163m-Nectin-4 negative tumors (74.8%) showed high cytoplasmic expression of Nectin-4 (c-Nectin-4(High)). At Kaplan-Meier analysis, m-Nectin-4 positivity was significantly associated with a lower disease-free survival (DFS) and distant relapse-free survival (DRFS) rate in patients with a luminal-A phenotype (P=0.030 and P=0.002, respectively). Multivariate analysis showed that in luminal-A tumors m-Nectin-4 positivity is an independent prognostic factor for DFS (P=0.018) and DRFS (P=0.004), but not for local relapse-free survival (LRFS). On the other hand, c-Nectin-4(High) was significantly associated with higher rates of DFS and LRFS, but not DRFS, in the whole population (P=0.008 and P=0.004, respectively) and in patients with luminal-A tumors (P=0.022 and P=0.018, respectively). In patients with luminal-A tumors, multivariate analysis showed that the prognostic value of c-Nectin-4(Low/Negative) is limited to DFS (P=0.012) and LRFS (P=0.022). We suggest that Nectin-4 represents a prognostic factor and a therapeutic target in luminal-A early stage breast cancer.

Nectin

Tissue microarray

10.1038/oncsis.2014.32

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Citations (44)

Additional file 1: of Effects of repurposed drug candidates nitroxoline and nelfinavir as single agents or in combination with erlotinib in pancreatic cancer cells

Figshare (2018)

Serena Veschi Laura De Lellis Rosalba Florio Paola Lanuti Alberto Massucci

Table S1. Effects of erlotinib, nelfinavir and nitroxoline as single agents versus drug combinations on cell viability. (XLSX 12 kb)

Nelfinavir

10.6084/m9.figshare.7120358

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Citations (0)

Impact of primary tumor location in patients with RAS wild-type metastatic colon cancer treated with first-line chemotherapy plus anti-EGFR or anti-VEGF monoclonal antibodies: a retrospective multicenter study

Journal of Cancer (2019)

Antonino Grassadonia Pietro Di Marino Corrado Ficorella Alessio Cortellini Katia Cannita

Emerging evidence supports a prognostic role of primary tumor location in metastatic colon cancer (mCC). We conducted a retrospective analysis to evaluate the effect of tumor location on prognosis and efficacy of biological agents (anti-EGFR, Cetuximab and Panitumumab, or anti-VEGF, Bevacizumab) added to first-line chemotherapy in patients with RAS wild-type (wt) mCC. Patients with newly diagnosed RAS wt mCC candidates to first-line chemotherapy with anti-EGFRs or Bevacizumab were selected. Clinical outcomes were assessed and stratified by tumor location and type of treatment. Overall, 351 patients met the inclusion criteria. Primary colon cancer was right-sided (RCC) in 105 (29.9%) patients and left-sided (LCC) in 246 (70.1%). Patients with LCC had a better OS compared to those with RCC (33.6 vs 23.5 months, HR 0.74; 95% CI, 0.55 to 0.99; p=0.049). In the overall study population, OS was not significantly different for patients treated with Cetuximab or Panitumumab as compared to those receiving Bevacizumab. However, when comparing treatment outcome according to tumor sidedness, patients with LCC treated with Cetuximab or Panitumumab had a significantly longer PFS (12.4 vs 10.7 months; HR: 0.69; 95% CI, 0.51 to 0.93; p= 0.015) and OS (40.7 vs 28.6 months; HR: 0.67; 95% CI 0.47 to 0.95; p= 0.026). No relevant differences were observed in patients with RCC. We found evidence in support of the impact of tumor location in RAS wt mCC treated with first-line chemotherapy in association with targeted therapy. More favorable outcomes were observed in LCC patients, but not in RCC patients, treated with anti-EGFR agents compared with those who received Bevacizumab. Further, prospective and adequately sized studies are warranted to confirm our findings.

Panitumumab

Primary tumor

10.7150/jca.34550

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Citations (29)